biostudies-literatureSimon LBundesministerium für Bildung und ForschungDeutscher Akademischer AustauschdienstThüringer AufbaubankDeutsche ForschungsgemeinschaftAgence Nationale de la RechercheEuropean Regional Development Funde2400148https://www.ebi.ac.uk/biostudies/studies/S-EPMC11648592biostudies-literatureUnknown24(12)Due to the increasing challenges posed by the growing immunity to poly(ethylene glycol) (PEG), there is growing interest in innovative polymer-based materials as viable alternatives. In this study, the advantages of lipids and polymers are combined to allow efficient and rapid cytoplasmic drug delivery. Specifically, poly(2-methyl-2-oxazoline) is modified with a cholesteryl hemisuccinate group as a lipid anchor (CHEMSPOx). The CHEMSPOx is additionally functionalized with a coumarin group (CHEMSPOx-coumarin). Both polymers self-assembled in water into vesicles of ≈100 nm and are successfully loaded with a hydrophobic model drug. The loaded vesicles reveal high cellular internalization across variant cell lines within 1 h at 37 °C as well as 4 °C, albeit to a lesser extent. A kinetic study confirms the fast internalization within 5 min after the sample's addition. Therefore, different internalization pathways are involved, e.g., active uptake but also nonenergy dependent mechanisms. CHEMSPOx and CHEMSPOx-coumarin further demonstrate excellent cyto-, hemo-, and membrane compatibility, as well as a membrane-protecting effect, which underlines their good safety profile for potential biological intravenous application. Overall, CHEMSPOx, as a lipopolyoxazoline, holds great potential for versatile biological applications such as fast and direct intracellular delivery or cellular lysis protection.Macromolecular biosciencePolyoxazolines with Cholesterol Lipid Anchor for Fast Intracellular Delivery.PMC11648592ANR-20-CE09-0011-013582630732018FGI002513XP5034A3162139872021 FGI 000557604510514006196Eberhardt JSimon LBrendel JCReichel LSMorille MSchubert USDevoisselle JMTraeger ACatrouillet SHoeppener SLapinte VBenkhaled BTfalsePolyoxazolines with Cholesterol Lipid Anchor for Fast Intracellular Delivery.Due to the increasing challenges posed by the growing immunity to poly(ethylene glycol) (PEG), there is growing interest in innovative polymer-based materials as viable alternatives. In this study, the advantages of lipids and polymers are combined to allow efficient and rapid cytoplasmic drug delivery. Specifically, poly(2-methyl-2-oxazoline) is modified with a cholesteryl hemisuccinate group as a lipid anchor (CHEMSPOx). The CHEMSPOx is additionally functionalized with a coumarin group (CHEMSPOx-coumarin). Both polymers self-assembled in water into vesicles of ≈100 nm and are successfully loaded with a hydrophobic model drug. The loaded vesicles reveal high cellular internalization across variant cell lines within 1 h at 37 °C as well as 4 °C, albeit to a lesser extent. A kinetic study confirms the fast internalization within 5 min after the sample's addition. Therefore, different internalization pathways are involved, e.g., active uptake but also nonenergy dependent mechanisms. CHEMSPOx and CHEMSPOx-coumarin further demonstrate excellent cyto-, hemo-, and membrane compatibility, as well as a membrane-protecting effect, which underlines their good safety profile for potential biological intravenous application. Overall, CHEMSPOx, as a lipopolyoxazoline, holds great potential for versatile biological applications such as fast and direct intracellular delivery or cellular lysis protection.2024-01-01T00:00:00Z2024 Dec2025-04-18T12:57:29.375Z2025-04-06T22:25:33.517ZS-EPMC116485923937434810.1002/mabi.202400148